Radiolabeled compounds are important tools in medical diagnosis and treatment. Such compounds are employed in a variety of techniques, including the diagnosis of deep venous thrombi; the study of lymph node pathology; and the detection, staging, and treatment of neoplasms. A number of these compounds employ metal radionuclides such as Technetium-99m. Radiolabeling of small molecules of various chemical structures to form metal radionuclide chelates has been described. Certain of these chelates are administered per se for medical purposes (e.g., diagnostic imaging). Other chelating compounds may be bound in vitro to proteins such as antibodies, then radiolabeled to form metal radionuclide chelate-protein conjugates, in efforts to deliver the radionuclide to a specific target site within a mammal. Alternatively, the chelate may be formed prior to attachment to a protein to form the conjugate.
Several such chelates comprise a metal radionuclide bound through covalent bonds to atoms of the chelating compound generally chosen from sulfur, nitrogen, or oxygen atoms, occasionally phosphorus atoms, or combinations thereof. In the case of chelating compounds comprising one or more sulfur atoms, various chemical groups generally are attached to the sulfur atoms as sulfur protective groups. These groups prevent undesired reactions of the sulfur atoms during synthesis of the chelating compounds and prior to the radiolabeling step. Radiolabeling of such chelating compounds has been accomplished by various methods which often have involved multistep procedures and/or separate steps for removal of the sulfur-protective groups prior to the radiolabeling reaction.
In view of the efforts underway to develop metal radionuclide chelates for medical use, a need for simple, efficient methods of radiolabeling chelating compounds to form the corresponding chelates is needed.
Publications of interest include: Khaw et al., J. Nucl. Med. (1982) 23:1011; Rhodes, B. A., Sem. Nucl. Med. (1974) 4:281; Davidson et al., Inorg. Chem. (1981) 20:1629; Byrne and Tolman, J. Nucl. Med. (1983) 24:126; Fritzberg et al., J. Nucl. Med. (1982) 23:592; Fritzberg et al., ibid. (1981) 22:258; Fritzberg et al., ibid. (1982) 23:17; U.S. Pat. Nos. 4,440,690, and 4,673,562.